Molecular BiotechnologyPub Date : 2025-07-01Epub Date: 2024-07-09DOI: 10.1007/s12033-024-01230-6
Raphaela Bento, Jürgen Scheller, Biju Parekkadan
{"title":"Intratumoral Delivery of Genetically Engineered Anti-IL-6 Trans-signaling Therapeutics.","authors":"Raphaela Bento, Jürgen Scheller, Biju Parekkadan","doi":"10.1007/s12033-024-01230-6","DOIUrl":"10.1007/s12033-024-01230-6","url":null,"abstract":"<p><p>Interleukin-6 (IL-6) is a highly pro-inflammatory cytokine involved in the etiopathology of several inflammatory diseases and cancer. As so, the inhibition of IL-6 signaling pathways has emerged as an attractive therapeutic avenue for the treatment of several chronic diseases. Since IL-6 trans-signaling was described as the pathological branch of IL-6, selective inhibitors were developed. Next-generation variants with increased trans-signaling specificity and potency emerged as great candidates for the treatment of several diseases, with reduced off-target effects. The highly time-consuming and costly processes involving recombinant protein production, however, have hampered the progress of anti-cytokine pharmaceuticals in clinic so far. Herein, we developed gene therapeutic modalities of IL-6-trans-signaling inhibitors as alternatives for sustained recombinant protein secretion. By using an IL-6-dependent lymphoma cell line and xenograft tumor model, we demonstrated the superior inhibitory potential of second-generation anti-IL-6 trans-signaling therapeutic. We compared the efficiency of distinct gene delivery modalities using a bioluminescent biomarker probe and observed consistent protein production via cell-based delivery. When delivered intratumorally, genetically engineered sgp130<sup>FlyR</sup>Fc-secreting cells significantly reduced tumor burden and increased animal survival, representing a promising therapeutic avenue to be explored in clinically relevant gene delivery applications.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2696-2708"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2025-07-01Epub Date: 2024-08-08DOI: 10.1007/s12033-024-01244-0
Yanjun Qiao, Ming Gu, Xiaowei Wang, Rui Chen, Lingchao Kong, Shuaitong Li, Jiaqi Li, Qingkun Liu, Sibing Hou, Zeying Wang
{"title":"Revealing Dynamics of Protein Phosphorylation: A Study on the Cashmere Fineness Disparities in Liaoning Cashmere Goats.","authors":"Yanjun Qiao, Ming Gu, Xiaowei Wang, Rui Chen, Lingchao Kong, Shuaitong Li, Jiaqi Li, Qingkun Liu, Sibing Hou, Zeying Wang","doi":"10.1007/s12033-024-01244-0","DOIUrl":"10.1007/s12033-024-01244-0","url":null,"abstract":"<p><p>Exploring the landscape of protein phosphorylation, this investigation focuses on skin samples from LCG (Liaoning Cashmere Goats), characterized by different levels of cashmere fineness. Employing LC-MS/MS technology, we meticulously scrutinized FT-LCG (fine-type Liaoning Cashmere Goats) and CT-LCG (coarse-type Liaoning Cashmere Goats). Identifying 512 modified proteins, encompassing 1368 phosphorylated peptide segments and 1376 quantifiable phosphorylation sites, our exploration further revealed consistent phosphorylation sites in both groups. Analysis of phosphorylated peptides unveiled kinase substrates, prominently featuring Protein Kinase C, Protein Kinase B and MAPK3-MAPK1-MAPK7-NLK-group. Differential analysis spotlighted 28 disparate proteins, comprising six upregulated and twenty-two downregulated. Cluster analysis showcased the robust clustering efficacy of the two sample groups. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses underscored the significance of the purine metabolism pathway, suggesting its pivotal role in modulating cashmere fineness in LCG. Notably, through differential protein analysis, two crucial proteins were identified: HSL-X (hormone-sensitive lipase isoform X1) and KPRP (keratinocyte proline-rich protein). Further evidence supports LIPE and KPRP as key genes regulating cashmere fineness, paving the way for promising avenues in further research. These findings not only contribute to a nuanced understanding of protein-level dynamics in cashmere but also provide a theoretical foundation for the selective breeding of superior Liaoning Cashmere Goat strands.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2832-2845"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2025-07-01Epub Date: 2024-07-14DOI: 10.1007/s12033-024-01236-0
Shreya Satyanarayan Bhat, Spoorthi R Kulkarni, Akshay Uttarkar, Vidya Niranjan
{"title":"Computational Insights into Papaveroline as an In Silico Drug Candidate for Alzheimer's Disease via Fyn Tyrosine Kinase Inhibition.","authors":"Shreya Satyanarayan Bhat, Spoorthi R Kulkarni, Akshay Uttarkar, Vidya Niranjan","doi":"10.1007/s12033-024-01236-0","DOIUrl":"10.1007/s12033-024-01236-0","url":null,"abstract":"<p><p>Alzheimer's disease (AD) poses a significant global health challenge, necessitating the exploration of novel therapeutic strategies. Fyn Tyrosine Kinase has emerged as a key player in AD pathogenesis, making it an attractive target for drug development. This study focuses on investigating the potential of Papaveroline as a drug candidate for AD by targeting Fyn Tyrosine Kinase. The research employed high-throughput virtual screening and QSAR analysis were conducted to identify compounds with optimal drug-like properties, emphasizing adherence to ADMET parameters for further evaluation. Molecular dynamics simulations to analyze the binding interactions between Papaveroline and Staurosporine with Fyn Tyrosine Kinase over a 200-ns period. The study revealed detailed insights into the binding mechanisms and stability of the Papaveroline-Fyn complex, showcasing the compound's potential as an inhibitor of Fyn Tyrosine Kinase. Comparative analysis with natural compounds and a reference compound highlighted Papaveroline's unique characteristics and promising therapeutic implications for AD treatment. Overall, the findings underscore Papaveroline's potential as a valuable drug candidate for targeting Fyn Tyrosine Kinase in AD therapy, offering new avenues for drug discovery in neurodegenerative diseases. This study contributes to advancing our understanding of molecular interactions in AD pathogenesis and paves the way for further research and development in this critical area.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2743-2757"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CircABHD2 Inhibits Malignant Progression of Endometrial Cancer by Regulating NAD<sup>+</sup>/NAMPT Metabolism Axis.","authors":"Huixin Li, Hanzi Xu, Mengyu Liu, Yang Li, Shenglong Yuan, Ping Yin, Zhen Gong, Shanliang Zhong","doi":"10.1007/s12033-024-01226-2","DOIUrl":"10.1007/s12033-024-01226-2","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) perform important functions in the regulation of diverse physiological and pathological processes. CircABHD2 exhibits down-regulation in both endometrial cancer (EC) cells and tissues, but the biological roles and mechanisms of action in EC are still unclear. This study aims to provide a theoretical basis for the role of circABHD2 in EC and potential targets for individualized precision therapy. Dysregulated circRNAs were identified using RNA sequencing (RNA-Seq) from EC tissues and validated using RT-qPCR. CCK-8, colony formation assay, wound healing assay, transwell assay, cell cycle, and apoptosis assay were used to evaluate the effects of circABHD2 on EC cells. Metabolomics assay and western blot analyses were used to investigate the potential mechanisms of circABHD2. From sequencing of RNA (RNA-Seq) analysis of EC tissues, we obtained 19 dysregulated circRNAs, including 8 upregulated ones and 11 downregulated ones. Using RT-qPCR on 32 EC tissues and 19 normal endometrial tissues, we confirmed that circABHD2 was downregulated in EC tissues. The expression levels of circABHD2 were closely relevant to the International Federation of Gynecology and Obstetrics (FIGO) stage and differentiation degree of EC. Functional experiments demonstrated that overexpression of circABHD2 decreased proliferation, migration, invasion, and promoted cell apoptosis. Un-targeted metabolomic assay revealed 31 differential metabolites in EC cells overexpressing circABHD2. KEGG analysis of differential metabolites indicated that NAD<sup>+</sup> is the core metabolite regulated by circABHD2. NAMPT is one key enzyme involved in the synthetic pathway responsible for NAD<sup>+</sup>. Subsequent experiments confirmed that by inhibiting NAMPT protein expression in EC cells, cirABHD2 can inhibit NAD<sup>+</sup> level, suggesting that circABHD2 may inhibit EC by regulating the metabolic axis of NAD<sup>+</sup>/NAMPT. CircABHD2, a downregulated circRNA in EC cells and tissues, inhibits the malignant progression of EC via the NAD<sup>+</sup>/NAMPT metabolic axis. This discovery presents a promising diagnostic biomarker and potential therapeutic target for EC.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2644-2659"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2025-07-01Epub Date: 2024-07-13DOI: 10.1007/s12033-024-01235-1
Jie Jiang, Ruoyu Hu, Zhuoshuan Li, Wei He
{"title":"Antibody MYH9 and Antibiotic Lidamycin Inhibit the Growth and Proliferation of Lung Cancer Cells and Induce Their Apoptosis.","authors":"Jie Jiang, Ruoyu Hu, Zhuoshuan Li, Wei He","doi":"10.1007/s12033-024-01235-1","DOIUrl":"10.1007/s12033-024-01235-1","url":null,"abstract":"<p><p>The aim of this study was to investigate the impact of the antibiotic lidamycin (LDM) and the targeted therapy with the antibody Myosin heavy chain 9 (MYH9) on cancer cells, aiming to provide insights for cancer treatment. In this study, antibiotics and targeted antibodies were used in cancer cells, and then their effects on cell growth, proliferation, apoptosis regulation, and related proteins were measured, and comparative analysis was conducted on the effects of different drug concentrations on the growth of cancer cells. In H460, the apoptotic effect of 2 nM LDM on cells reached 70%. LDM had a downward trend on the levels of B-cell lymphoma-2 (Bcl-2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in cells. The inhibitory effects of LDM at different concentrations on human large cell lung cancer H460 transplanted tumor in nude mice reached 53.20% and 69.80%, and the inhibitory effects on the growth of lung adenocarcinoma transplanted tumor in nude mice reached 40.20% and 58.30%. The expression of MYH9 (myosin, heavy polypeptide 9, non-muscle) in human lung cancer tissues and adjacent tissues reached more than 80%. At the concentration of 300 μM, antibody MYH9 inhibited cell growth by 30%, and the migration rate was also reduced by 25%. The inhibitory effect of siRNA after knocking out the MYH9 gene on cancer cells reached 70%. Antibiotic LDM and targeted antibody MYH9 can inhibit the growth, proliferation, and migration of cancer cells, promote cancer cell apoptosis, and have certain clinical significance for the treatment of cancer patients.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2732-2742"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2025-07-01Epub Date: 2024-07-24DOI: 10.1007/s12033-024-01241-3
Anagha S Setlur, Vidya Niranjan, Chandrashekar Karunakaran, Varun S Sambanni, Dileep Sharma, Karthik Pai
{"title":"Unified Aedes aegypti Protein Resource Database (UAAPRD): An Integrated High-Throughput In Silico Platform for Comprehensive Protein Structure Modeling and Functional Target Analysis to Enhance Vector Control Strategies.","authors":"Anagha S Setlur, Vidya Niranjan, Chandrashekar Karunakaran, Varun S Sambanni, Dileep Sharma, Karthik Pai","doi":"10.1007/s12033-024-01241-3","DOIUrl":"10.1007/s12033-024-01241-3","url":null,"abstract":"<p><p>A comprehensive examination of Aedes aegypti's proteome to detect key proteins that can be targeted with small molecules can disrupt blood feeding and disease transmission. However, research currently only focuses on finding repellent-like compounds, limiting studies on identifying unexplored proteins in its proteome. High-throughput analysis generates vast amounts of data, raising concerns about accessibility and usability. Establishing a dedicated database is a solution, centralizing information on identified proteins, functions, and modeled structures for easy access and research. This study focuses on scrutinizing key proteins in A. aegypti, modeling their structures using RaptorX standalone tool, identification of druggable binding sites using BiteNet, validating the models via Ramachandran plot studies and refining them via 50-ns molecular dynamic simulations using Schrodinger Maestro. By analyzing ~ 18 k proteins in the proteome of A. aegypti in our previous studies, all proteins involved in the light and dark circadian rhythm of the mosquito, inclusive of proteins in blood feeding, metabolism, etc. were chosen for the current study. The outcome is UAAPRD, a unique repository housing information on hundreds of previously unmodeled and un-simulated mosquito proteins. This robust MYSQL database ( https://uaaprd.onrender.com/user ) houses data on 309 modeled & simulated proteins of A. aegypti. It allows users to obtain protein data, view evolutionary analysis data of the protein categories, visualize proteins of interest, and send request to screen against the pharmacophore models present in UAAPRD against ligand of interest. This study offers crucial insights for developing targeted studies, which will ultimately contribute to more effective vector control strategies.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2798-2816"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2025-07-01Epub Date: 2024-07-02DOI: 10.1007/s12033-024-01233-3
Yangyang Xiao, Youwen Hu
{"title":"Comprehensive Bioinformatics Analysis and Machine Learning of TTK as a Transhepatic Arterial Chemoembolization Resistance Target in Hepatocellular Carcinoma.","authors":"Yangyang Xiao, Youwen Hu","doi":"10.1007/s12033-024-01233-3","DOIUrl":"10.1007/s12033-024-01233-3","url":null,"abstract":"<p><p>Transhepatic arterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, a significant proportion of patients are non-responders or poor responders to TACE. Therefore, our aim is to identify the targets of TACE responders or non-responders. GSE104580 was utilized to identify differentially expressed genes (DEGs) in TACE responders and non-responders. Following the protein-protein interaction (PPI) analysis, hub genes were identified using the MCC and MCODE plugins in Cytoscape software, as well as LASSO regression analysis. Gene set enrichment analysis (GSEA) was performed to investigate potential mechanisms. Subsequently, the hub genes were validated using data from The Cancer Genome Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE), and The Human Protein Atlas (HPA) database. To evaluate the clinical significance of the hub genes, Kaplan-Meier (KM) survival and Cox regression analysis were employed. A total of 375 DEGs were identified, with 126 remaining following PPI analysis, and TTK, a dual-specificity protein kinase associated with cell proliferation, was ultimately identified as the hub gene through multiple screening methods. Data analysis from TCGA, CCLE, and HPA databases revealed elevated TTK expression in HCC tissues. GSEA indicated that the cell cycle, farnesoid X receptor pathway, PPAR pathway, FOXM1 pathway, E2F pathway, and ferroptosis could be potential mechanisms for TACE non-responders. Analysis of immune cell infiltration showed a significant correlation between TTK and Th2 cells. KM and Cox analysis suggested that HCC patients with high TTK expression had a worse prognosis. TTK may play a pivotal role in HCC patients' response to TACE therapy and could be linked to the prognosis of these patients.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2720-2731"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prospects of Innovative Therapeutics in Combating the COVID-19 Pandemic.","authors":"Thamby Rajah Mahendran, Binsin Cynthia, Ramesh Thevendran, Solayappan Maheswaran","doi":"10.1007/s12033-024-01240-4","DOIUrl":"10.1007/s12033-024-01240-4","url":null,"abstract":"<p><p>The sudden global crisis of COVID-19, driven by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), demands swift containment measures due to its rapid spread and numerous problematic mutations, which complicate the establishment of herd immunity. With escalating fatalities across various nations no foreseeable end in sight, there is a pressing need to create swiftly deployable, rapid, cost-effective detection, and treatment methods. While various steps are taken to mitigate the transmission and severity of the disease, vaccination is proven throughout mankind history as the best method to acquire immunity and circumvent the spread of infectious diseases. Nonetheless, relying solely on vaccination might not be adequate to match the relentless viral mutations observed in emerging variants of SARS-CoV-2, including alterations to their RBD domain, acquisition of escape mutations, and potential resistance to antibody binding. Beyond the immune system activation achieved through vaccination, it is crucial to develop new medications or treatment methods to either impede the infection or enhance existing treatment modalities. This review emphasizes innovative treatment strategies that aim to directly disrupt the virus's ability to replicate and spread, which could play a role in ending the SARS-CoV-2 pandemic.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2598-2606"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2025-07-01Epub Date: 2024-07-11DOI: 10.1007/s12033-024-01231-5
Shun Gao, Li Li, Yonggong Wei, Lei Wen, Shujuan Shao, Jianhang Wu, Xuyan Zong
{"title":"Research Progress of ARTP Mutagenesis Technology Based on Citespace Visualization Analysis.","authors":"Shun Gao, Li Li, Yonggong Wei, Lei Wen, Shujuan Shao, Jianhang Wu, Xuyan Zong","doi":"10.1007/s12033-024-01231-5","DOIUrl":"10.1007/s12033-024-01231-5","url":null,"abstract":"<p><p>Atmospheric and room temperature plasma (ARTP) mutagenesis technology has been developed rapidly in recent years because of its simple operation, safety, environmental friendliness, high mutation rate, and large mutation library capacity. It has been widely used in traditional fields such as food, agriculture, and medicine, and has been gradually applied in emerging fields such as environmental remediation, bioenergy, and microalgae utilization. In this paper, the Web of Science Core Collection (WOSCC) was used as the data source, and the keywords and core literature of ARTP mutagenesis technology were plotted by citespace software, and the research progress and research hotspots of ARTP mutagenesis technology were analyzed. Through citespace visualization analysis, it is concluded that the country with the largest number of studies is China, the institution with the largest number of studies is Jiangnan University, and the author of the most published papers is Jiangnan University. Through keyword analysis, it is concluded that the most widely used ARTP mutagenesis technology is fermentation-related majors, mainly for biosynthesis and microbial research at the molecular level. Among them, the most widely used microorganisms are Escherichia coli and Saccharomyces cerevisiae.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2587-2597"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Molecular BiotechnologyPub Date : 2025-07-01Epub Date: 2024-07-18DOI: 10.1007/s12033-024-01237-z
Chengru Chen, Peng Zou, Xiaobin Wu
{"title":"Development and Validation of an Immune Prognostic Index Related to Infiltration of CD4+ and CD8+ T Cells in Colorectal Cancer.","authors":"Chengru Chen, Peng Zou, Xiaobin Wu","doi":"10.1007/s12033-024-01237-z","DOIUrl":"10.1007/s12033-024-01237-z","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a highly prevalent cancer worldwide, but treatment outcomes can vary significantly among patients with similar clinical or historical stages. This study aimed to investigate the differences in immune cell abundance associated with malignant progression in CRC patients. We utilized data from patients with CRC obtained from The Cancer Genome Atlas as our training set. To assess immune cell infiltration levels, an immune cell risk score (ICRS) was calculated. Furthermore, we performed network analysis to identify effective T cell-related genes (ETRGs) and subsequently constructed an effective T cell prognostic index (ETPI). The performance of the ETPI was evaluated through external validation using four Gene Expression Omnibus datasets. Additionally, a nomogram analysis and drug sensitivity analysis were conducted to explore the clinical utility of the ETRGs. We also examined the expression of ETRGs in clinical samples. Based on the ICRS, we identified activated CD4+ and CD8+ T cells as protective factors in terms of prognosis. Six ETRGs were identified to develop the ETPI, which exhibited remarkable prognostic performance. In the external validation of immunotherapy, the low ETPI group demonstrated a significantly lower recurrence rate. To optimize therapeutic strategies, we developed a nomogram. Notably, patients with different ETPI values exhibited varying responses to tumor pathway inhibitors. Finally, we observed higher protein expression of certain ETRGs in normal tissues compared to tumors. Our findings suggest that the ETPI may contribute to the precise selection of patients based on tumor microenvironment and key genomic landscape interactions, thereby optimizing drug benefits and informing clinical strategies in future.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"2758-2773"},"PeriodicalIF":2.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}